{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T15:22:56Z","timestamp":1777648976569,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology in Taiwan","doi-asserted-by":"crossref","award":["107-2636-B-009-001"],"award-info":[{"award-number":["107-2636-B-009-001"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology in Taiwan","doi-asserted-by":"crossref","award":["105-2118-M-001-014-MY3"],"award-info":[{"award-number":["105-2118-M-001-014-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2019,6,15]]},"abstract":"<jats:p>Agonistic interaction is one of the most important types of mechanistic interaction, which is difficult to be distinguished from synergistic interaction by empirical data. In this study, we propose four approaches that suffice to identify and estimate the agonistic interaction: (1) to make a strong assumption that synergism does not exist; (2) to exploit information from a third factor by assuming that this factor is a necessary component for the background condition of synergistic interaction but is not involved in other mechanisms; (3) to consider a third factor necessary for the background condition of agonistic interaction but not involved in other mechanisms; and (4) similar to (3) but to allow flexibility that the third factor may have a main effect on the outcome and\/or a synergistic effect with the two risk factors of interest. We applied the proposed methods to quantify the agonism of Hepatitis B and C viruses (HBV and HCV) infections on liver cancer using a Taiwanese cohort study (<jats:italic>n<\/jats:italic>\u00a0=\u00a023\u2009820; HBV carrier <jats:italic>n<\/jats:italic>\u00a0=\u00a04149 (17.44%), HCV carrier <jats:italic>n<\/jats:italic>\u00a0=\u00a01313 (5.52%)). The result demonstrated that agonistic interaction is more dominant compared with synergistic interaction, which explains the findings that the dual infected patients do not have a significantly higher risk of liver cancer than those with single infection. By exploiting an additional risk factor that satisfies certain assumptions, these approaches potentially fill the gap between mechanistic and causal interactions, contributing the comprehensive understanding of causal mechanisms.<\/jats:p>","DOI":"10.1002\/sim.8123","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T07:01:03Z","timestamp":1551942063000},"page":"2467-2476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["On identification of agonistic interaction: Hepatitis B and C interaction on hepatocellular carcinoma"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-2354","authenticated-orcid":false,"given":"Sheng\u2010Hsuan","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Statistics National Chiao Tung University  Hsinchu Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7657-0040","authenticated-orcid":false,"given":"Yen\u2010Tsung","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Statistical Science Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hwai\u2010I","family":"Yang","sequence":"additional","affiliation":[{"name":"Genomics Research Center Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,6]]},"reference":[{"key":"e_1_2_5_2_1","volume-title":"Explanation in Causal Inference: Methods for Mediation and Interaction","author":"VanderWeele T","year":"2015"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.2307\/1403235"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.5271\/sjweh.1945"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000260218.66432.88"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a112335"},{"key":"e_1_2_5_7_1","volume-title":"Modern Epidemiology","author":"Rothman KJ","year":"2008"},{"key":"e_1_2_5_8_1","unstructured":"LinSH HuangYT LeeWC.Visualization of agonistic interaction through an exclusive transformation of sufficient component cause model. Submitting."},{"key":"e_1_2_5_9_1","volume-title":"Human Pharmacology: Molecular to Clinical","author":"Brody TM","year":"1998"},{"key":"e_1_2_5_10_1","doi-asserted-by":"crossref","first-page":"e0121638","DOI":"10.1371\/journal.pone.0121638","article-title":"Testing for mechanistic interactions in long\u2010term follow\u2010up studies","volume":"10","author":"Lin J\u2010H","year":"2015","journal-title":"PloS One"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e318277f122"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067424"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.2335"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450107"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.2.74"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008951901148"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwg041"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890110302"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840220413"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890450222"},{"issue":"10","key":"e_1_2_5_21_1","doi-asserted-by":"crossref","first-page":"5823","DOI":"10.1128\/jvi.67.10.5823-5832.1993","article-title":"Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH\u20107 cells","volume":"67","author":"Shih CM","year":"1993","journal-title":"J Virol"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00296-9"},{"key":"e_1_2_5_23_1","volume-title":"Hepatitis Viruses","author":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans","year":"1994"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890310021580"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2004.00521.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e31824ea1d8"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1214\/09-SS057"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jech.2002.006361"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-985X.2007.00527.x"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-3758(90)90077-8"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2002.00021.x"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a114211"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780080709"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr009"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0377-2217(84)90282-0"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.2307\/2344614"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.1.65"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.03.073"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.06.015"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.29.1500"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.4300"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-7397-5_1"}],"container-title":["Statistics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fsim.8123","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.8123","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sim.8123","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.8123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T18:48:00Z","timestamp":1694371680000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/sim.8123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,6]]},"references-count":41,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2019,6,15]]}},"alternative-id":["10.1002\/sim.8123"],"URL":"https:\/\/doi.org\/10.1002\/sim.8123","archive":["Portico"],"relation":{},"ISSN":["0277-6715","1097-0258"],"issn-type":[{"value":"0277-6715","type":"print"},{"value":"1097-0258","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,6]]},"assertion":[{"value":"2018-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}